Magnetic resonance imaging (mri) contrast agents and use thereof

Abstract

A hybrid molecule comprising at least one contrast agent, and at least one substrate of a self-labeling enzyme, and optionally a fluorescent moiety is provided. Compositions comprising same and use thereof, are also provided.

1 . A hybrid molecule comprising at least one contrast agent and at least one substrate of a self-labeling enzyme. 
     
     
         2 . The hybrid molecule of  claim 1 , further comprising at least one fluorescent moiety. 
     
     
         3 . The hybrid molecule of  claim 1 , wherein said at least one contrast agent is selected from: (i) a radiocontrast agent; (ii) contrast agent selected from the group consisting of a T1-class and a T2-class MRI contrast agent; (iii) an iodine based contrast agent; and (iv) a contrast agent comprising a metal selected from the group consisting of: a superparamagnetic metal, a paramagnetic metal, a diamagnetic metal, a ferromagnetic metal, or any combination thereof. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The hybrid molecule of  claim 3 , wherein any one of (i) said at least one paramagnetic metal is selected from the group consisting of Barium (Ba), Tantalum (Ta), Tungsten (W), Dysprosium (Dy), Platinium (Pt), Gadolinium (Gd), and Manganese (Mn); (ii) said at least one diamagnetic metal is selected from the group consisting of Bismuth (Bi) and Gold (Au); and (iii) said ferromagnetic metal is iron (Fe). 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The hybrid molecule of  claim 1 , wherein said self-labeling enzyme is capable of covalently binding to said substrate. 
     
     
         11 . The hybrid molecule of  claim 10 , wherein said self-labeling enzyme is selected from the group consisting of: SNAP, CLIP and Halo, optionally wherein said substrate is selected from the group consisting of: O 6 -benzylguanine derivatives, O 2 -benzylcytosine derivatives, and chloroalkene derivatives. 
     
     
         12 . (canceled) 
     
     
         13 . The hybrid molecule of  claim 2 , wherein said fluorescent moiety is capable of emitting UV, visible, or near infrared light, optionally wherein said fluorescent moiety is selected from the group consisting of: green fluorescent protein (GFP) and Tomato. 
     
     
         14 . (canceled) 
     
     
         15 . The hybrid molecule of  claim 1 , wherein said molecule has the general Formula:
   (R) n —(F) m —(S) p ,
   wherein:   R represents said contrast agent;   F represents said fluorescent moiety, and   S represents said substrate,   wherein n and p are each, independently, an integer from 1 to 5 and m is an integer from 0-5.   
     
     
         16 . (canceled) 
     
     
         17 . A composition comprising the hybrid molecule of  claim 1 , and a pharmaceutically acceptable carrier, excipient or adjuvant. 
     
     
         18 . The composition of  claim 17 , comprising at least a first and a second hybrid molecule, wherein said substrate of said first hybrid molecule differs from said substrate of said second hybrid molecule, and at least one of said contrast agent and said fluorescent moiety of said first hybrid molecule differs from said contrast agent and said fluorescent moiety of said second hybrid molecule. 
     
     
         19 . A cell-specific imaging method, the method comprising:
 contacting one or more cells with a composition of  claim 17 , wherein at least one cell of said one or more cells expresses one or more self-labeling enzymes capable of binding to said substrate,   thereby imaging a specific cell.   
     
     
         20 . The method of  claim 19 , wherein said one or more cells express said one or more self-labeling enzymes on said at least one cell's surface. 
     
     
         21 . The method of  claim 19 , wherein said one or more cells are in the form of a tissue, optionally wherein said at least one cell is selected from a cancerous cell, a neuronal cell, and an immune cell. 
     
     
         22 . The method of  claim 19 , wherein said contacting is performed ex-vivo or in-vivo. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 19 , comprising a preliminary step of expressing within said at least one cell said self-labeling enzymes capable of binding to said substrate. 
     
     
         25 . The method of  claim 24 , wherein said expressing comprises introducing into said at least one specific cell one or more nucleic acid molecules comprising a polynucleotide sequence encoding said one or more self-labeling enzymes. 
     
     
         26 . The method of  claim 25 , wherein said polynucleotide sequence encoding said one or more self-labeling enzymes is operatively linked to a cell-specific promoter. 
     
     
         27 . The method of  claim 19 , further comprising applying a magnetic field, X-radiation, UV-vis light or any combination thereof, to said contacted cells. 
     
     
         28 . The method of  claim 27 , further comprising measuring or detecting said contrast agent, said fluorescent moiety or both. 
     
     
         29 . A kit comprising:
 (a) at least one hybrid molecule of  claim 1 ; and   (b) one or more nucleic acid constructs comprising a polynucleotide sequence encoding one or more self-labeling enzymes, optionally wherein said polynucleotide sequence encoding one or more self-labeling enzyme is operatively linked to a cell-specific promoter.   
     
     
         30 . (canceled)